# Evidence: phase-separated domain size

Parent: — · class: phase behaviour · names merged here: phase domain size; phase-separated domain size

4 papers measured or used it, 0 only mentioned it (of 207 kept papers). Papers in year order; each section heading ends with the paper's category / subcategory. Generated by tools/build_evidence.py from registry/concepts.csv and the cards; do not edit.

## 2015 Purohit — Miscibility of Itraconazole-Hydroxypropyl Methylcellulose Blends- Insights with High Resolution Analytical Methodologies · Solid state stability / Miscibility and drug-polymer interactions

[2015-purohit-itraconazole-hpmc-miscibility-high-resolution-methods](../../../cards/2015-purohit-itraconazole-hpmc-miscibility-high-resolution-methods/paper.html) · Solid state stability / Miscibility and drug-polymer interactions · measured · as: phase-separated domain size

| id | kind | content | locator |
|---|---|---|---|
| R10 | record, measured | AFM topography of films before heating; domain size — films 10:90 to 50:50 on ZnSe (P9); 40:60 film for nanoTA (P10) — text: phase-separated domains at all ratios; discrete domains of 500-1000 nm in a continuous phase. Figure readings: round raised domains (bright) in a darker continuous matrix; diameters ≈0.4-1.0 µm in 10:90 to 30:70 (Fig. 6a-c), ≈0.5-1.4 µm in 40:60 (Fig. 6d), ≈0.7-1.0 µm in 50:50 (Fig. 6e, 2.5 µm scan), ≈0.5-1.5 µm in the 20 µm scan of 40:60 (Fig. 8) (read from scale bars) | Figs. 6, 8, p.24-25, p.28; text p.13-14 |
| R14 | record, measured | AFM topography and nanoIR chemical image at 1700 cm⁻¹ — 30:70 film, 10 × 10 µm; height scale -500 to 500 nm; chemical image -0.1 to 0.1 V — red ITZ-rich round domains of ≈1.5-2.5 µm (read from the graphic) in a blue ITZ-lean continuous phase; raised domains in topography coincide with the red regions | TOC graphic, p.39 |
| C37 | claim, conclusion, authors: discussion: asserted ("reveals"); abstract: "indicated" (sub-micron scale); conclusions: asserted | The lower-viscosity component ITZ forms discrete drug-rich domains of 500-1000 nm in a drug-lean (HPMC) continuous phase; a lower-viscosity phase forming discrete domains was reported before [rests on: R10, R11, R13; cited: ref 40] | p.2; p.14; p.19 |
| X8 | extractor note | claim-data gap — C37 gives domains of 500-1000 nm, but some features read larger: ≈1.2-1.4 µm in Fig. 6d (40:60), up to ≈1.5 µm in Fig. 8, and ≈1.5-2.5 µm in the TOC chemical image of a 30:70 film; no size distribution is reported — C37, R10, R14 — treat domain size as ≈0.4 to ≈2.5 µm depending on film and location, not quantified |  |

## 2016 Li — Nanoscale Infrared, Thermal, and Mechanical Characterization of Telaprevir-Polymer Miscibility in Amorphous Solid Dispersions Prepared by Solvent Evaporation · Solid state stability / Miscibility and drug-polymer interactions

[2016-li-telaprevir-polymer-miscibility-nanoscale-afm-ir](../../../cards/2016-li-telaprevir-polymer-miscibility-nanoscale-afm-ir/paper.html) · Solid state stability / Miscibility and drug-polymer interactions · measured · as: phase-separated domain size

| id | kind | content | locator |
|---|---|---|---|
| R4 | record, measured | topography versus DL — TPV-HPMC films 1:9 to 5:5 (P1, P2), contact mode, 4 x 2 µm — text: discrete domains present at 10% DL; height features larger as DL increases; from 40% to 50% DL domains more irregular in shape and less uniform in size; domain height about 30 nm at 50% DL. Figure colour scales ±10 nm (1:9), ±25 nm (2:8 to 4:6), ±50 nm (5:5) | Fig. 3A, p.37; text p.13 |
| R5 | record, measured | topography versus DL — TPV-HPMCAS films 1:9 to 5:5 (P1, P2); 4 x 2 µm (1:9, 2:8), 5 x 2.51 µm (3:7, 5:5), 3 x 1.5 µm (4:6); colour scale ±25 nm — text: below 40% DL irregular height variations like those of the pure HPMCAS film; at 40% DL very small, regularly shaped circular domains about 120 nm in diameter and 50 nm in height; features more obvious at 50% DL | Fig. 3B, p.37; text p.13 |
| R6 | record, measured | topography versus DL — TPV-PVPVA films 1:9 to 5:5 (P1, P2); contact mode at 10-20% DL, tapping mode at 30-50% DL; 5 x 2.51 µm (1:9, 2:8), 4 x 2 µm (3:7 to 5:5) — text: discrete domains present at 10% DL; spacing between domains decreases as DL increases; surface rougher; domain diameter about 280 nm at 10% DL and 380 nm at 50% DL; domain height about 20 nm at 10% DL and 100 nm at 50% DL. Figure colour scales ±25, ±50, ±100, ±200 and ±100 nm for 1:9 to 5:5 | Fig. 3C, p.37; text p.13-14 |
| R7 | record, measured | domain dimensions stated in the text — TPV-HPMCAS and TPV-HPMC films (P2) — maximum distance among discrete domains 21 nm (40% DL) and 25 nm (50% DL) in TPV-HPMCAS; 50:50 TPV-HPMCAS domains 122 nm wide and 13 nm high (average domain size 122 nm); domain size below 50 nm in 10:90 TPV-HPMC and around 100-200 nm in the other TPV-HPMC and TPV-HPMCAS systems | p.15, p.25, p.26 |
| C42 | claim, generalisation, authors: "is likely to" | Domain size is likely to affect ASD performance during dissolution [rests on: argument only] | p.24 |
| C54 | claim, conclusion, authors: asserted | The drug-rich phase forms discrete domains from below 50 nm to a few hundred nanometres, depending on the system, in a polymer-rich continuous phase; such information is essential to relate microstructure to product performance [rests on: R4-R10, R13-R15, R22] | p.3, p.29 |

## 2016 Tian — Investigating the Correlation between Miscibility and Physical Stability of Amorphous Solid Dispersions Using Fluorescence-based Techniques · Solid state stability / Physical stability

[2016-tian-indomethacin-polymer-miscibility-physical-stability-fluorescence](../../../cards/2016-tian-indomethacin-polymer-miscibility-physical-stability-fluorescence/paper.html) · Solid state stability / Physical stability · used · as: phase domain size

| id | kind | content | locator |
|---|---|---|---|
| C7 | claim, prior hypothesis, authors: "probably"; asserted | DSC is the most common miscibility test (one Tg = miscible, two Tgs = two phases), but phase separation is hard to detect when domains are smaller than 30 nm, Tgs are similar or phases remix on heating; single Tgs in phase-separated systems and two Tgs in miscible systems have been reported [rests on: cited: refs 16-21] | p.3-4 |
| C44 | claim, caveat, authors: asserted | Fluorescence imaging is diffraction-limited; domains smaller than around 300-500 nm cannot be resolved [rests on: argument only] | p.23 |
| C45 | claim, generalisation, authors: "potentially" | The spectra report the local environment of IDM and domain formation is inferred from abrupt spectral changes, so the spectral approach is potentially sensitive to very small domains [rests on: R2, R3, R4] | p.23 |
| R23 | record, cited (ref 38) | miscibility of IDM-PVP by 1H T1ρ relaxation — IDM-PVP ASDs with 10-50 wt% polymer — miscible at a domain size of ~5 nm | p.24 |

## 2017 Purohit — Insights into Nano- and Micron-Scale Phase Separation in Amorphous Solid Dispersions Using Fluorescence-Based Techniques in Combination with Solid State Nuclear Magnetic Resonance Spectroscopy · Characterization methods / Solid-state methods

[2017-purohit-itraconazole-hpmc-asd-phase-separation-fluorescence-ssnmr](../../../cards/2017-purohit-itraconazole-hpmc-asd-phase-separation-fluorescence-ssnmr/paper.html) · Characterization methods / Solid-state methods · measured · as: phase-separated domain size

| id | kind | content | locator |
|---|---|---|---|
| R16 | record, measured | confocal distribution of probes, slow-evaporation film — 40:60 film cast on quartz, prodan + R6G, excitation 407 and 561 nm (P3, P10) — R6G signal mainly in the continuous phase, with dark unstained areas; prodan signal in discrete circular domains, large areas unstained; drug-rich (prodan) domains around 5 μm (text pdf p.7) and ~3–5 μm (text pdf p.11); larger prodan regions made of smaller aggregates (circled in Fig. 8); scale bar 20 μm | Fig. 8, pdf p.8; Results, pdf p.7; Discussion, pdf p.11 |
| R17 | record, measured | confocal distribution of probes, spin-coated film — 40:60 spin-coated film, prodan + R6G (P2, P10) — same distribution as R16 (prodan in discrete domains, R6G in continuous phase); drug-rich domains 1 μm (text pdf p.7) and ~400 nm–1 μm (text pdf p.11) | Fig. 8, pdf p.8; Results, pdf p.7; Discussion, pdf p.11 |
| R18 | record, derived (P10) | drug-rich domain size distribution (ImageJ) — spin-coated films (P2, P10) — smallest 300 nm; largest 2.8 μm; D50 0.9 μm; D90 1.5 μm; number of domains analysed not printed | Results, pdf p.7 |
| R21 | record, measured (T1, T1rho); derived (Δ by subtraction; domain size by E2) | 1H T1 and T1rho of ITZ and HPMC with spin-diffusion domain-size ranges (Table II, sub-table below) — SD ASD and film-cast ASD (P11, P12) — rows a–b below; averages of a few resolved peaks; standard errors in parentheses; the Miscibility column is given as claims C20 and C21 | Table II, pdf p.9 |
| R22 | record, derived (relation not printed) | domain size of phase-separated regions by preparation route (Table III, sub-table below) — 40:60 ASDs — rows a–c below | Table III, pdf p.10 |
| C43 | claim, conclusion, authors: asserted | Domain size of the phase-separated regions depended on solvent evaporation rate: smaller in SD ASDs, larger and more easily detected at slower evaporation (film cast > spin coated > spray dried). [rests on: R21, R22, R23, R16, R17] | Abstract, pdf p.1; Table III, pdf p.10; Discussion, pdf p.12; Conclusions, pdf p.12 |